Acta Clin Croat 2018; 57:342-351 Review

doi: 10.20471/acc.2018.57.02.16

DIFFERENTIAL DIAGNOSIS OF CHEILITIS

– HOW TO CLASSIFY CHEILITIS?
Liborija Lugović-Mihić1,2, Kristina Pilipović2, Iva Crnarić1,
Mirna Šitum1,2 and Tomislav Duvančić1

1
Department of Dermatovenereology, Sestre milosrdnice University Hospital Center, Zagreb, Croatia;
2
School of Dental Medicine, University of Zagreb, Zagreb, Croatia

SUMMARY – Although cheilitis as a term describing lip inflammation has been identified and
recognized for a long time, until now there have been no clear recommendations for its work-up and
classification. The disease may appear as an isolated condition or as part of certain systemic diseases/
conditions (such as anemia due to vitamin B12 or iron deficiency) or local infections (e.g., herpes and
oral candidiasis). Cheilitis can also be a symptom of a contact reaction to an irritant or allergen, or may
be provoked by sun exposure (actinic cheilitis) or drug intake, especially retinoids. Generally, the forms
most commonly reported in the literature are angular, contact (allergic and irritant), actinic, glandular,
granulomatous, exfoliative and plasma cell cheilitis. However, variable nomenclature is used and sub-
types are grouped and named differently. According to our experience and clinical practice, we suggest
classification based on primary differences in the duration and etiology of individual groups of cheili-
tis, as follows: 1) mainly reversible (simplex, angular/infective, contact/eczematous, exfoliative, drug-
related); 2) mainly irreversible (actinic, granulomatous, glandular, plasma cell); and 3) cheilitis con-
nected to dermatoses and systemic diseases (lupus, lichen planus, pemphigus/pemphigoid group,
angioedema, xerostomia, etc.).
Key words: Cheilitis; Inflammation; Lip Diseases; Actinic Cheilitis; Classification; Dermatitis, Contact

Introduction lated to the effects of irritants (climatic, mechanical,

The term cheilitis indicates inflammation of the lip
and includes many types, i.e. angular, contact, exfolia-
tive, actinic, glandular, granulomatous, plasma cell
cheilitis, simplex, etc.1-5. In practice, it is difficult to de-
fine readily the precise type of cheilitis, thus proper
diagnostic procedures are necessary to determine the
exact disease based on its characteristics5. For example,
angular cheilitis can occur spontaneously or may be
related to several precipitating factors (e.g., systemic
immune suppression, local irritation and moisture,
fungal/bacterial infection). Contact cheilitis can be re-
Correspondence to: Prof. Liborija Lugović-Mihić, MD, PhD, De-
partment of Dermatovenereology, Sestre milosrdnice University
Hospital Center, Vinogradska c. 29, HR-10000 Zagreb, Croatia
E-mail: liborija@gmail.com
Received August 28, 2017, accepted December 12, 2017
caustic agents) or allergens (allergic contact cheilitis)5.
Some types of cheilitis last longer and are persistent,
such as chronic actinic cheilitis, granulomatous
cheilitis and plasma cell cheilitis. Furthermore, cheili-
tis can also be seen in various skin or systemic diseases
such as lupus erythematosus, lichen planus, atopic
dermatitis, etc.
Cheilitis may also be associated with numerous
conditions or diseases, e.g., nutritional deficiencies,
such as megaloblastic anemia due to vitamin B12 defi-
ciency, anemia due to iron deficiency, oral candidiasis,
diabetes2,4-8.
Additionally, cheilitis is often divided into particu-
lar subtypes with no clear classification having yet
been adopted. Considering its duration, some authors
refer to acute or chronic cheilitis, whereby there are no

342 Acta Clin Croat, Vol. 57, No. 2, 2018

Liborija Lugović-Mihić et al. Differential diagnosis of cheilitis

Table 1. Proposed classification of cheilitis

In association with dermatoses and systemic
Mostly reversible Mostly persistent
diseases (common diseases)
Cheilitis simplex Actinic cheilitis Lupus erythematosus
Angular/infective cheilitis Granulomatous cheilitis Lichen planus
Contact/eczematous cheilitis Glandular cheilitis Angioedema
Exfoliative cheilitis Plasma cell cheilitis Pemphigoid/pemphigus
Drug related cheilitis Xerostomia
Erythema multiforme
Crohn’s disease
Sarcoidosis, etc.

Table 2. Prominent features of mostly reversible cheilitis

Mostly reversible
Occurrence Related factors Therapy
cheilitis
Cheilitis simplex Common Lip licking Advice on environmental conditions
Cold, windy, dry weather Application of lip balms, petroleum
jelly, emollients, topical
corticosteroids, ointments
Angular/infective Common
Infective agents Elimination of local predisposing
cheilitis Immune deficiency (diabetes, HIV) factors
Mechanical factors Topical antimycotics, antiseptics,
Nutritional deficiencies antibiotics, topical corticosteroids
(riboflavin, folate, iron, etc)
Contact/eczematous Very common Atopy, contact allergens/irritants Topical corticosteroids (low to
cheilitis medium potency), emollients
Exfoliative cheilitis Rare Lip licking/picking Corticosteroids
Psychological distress Psychotherapy
Nutritional deficiencies (some cases resolve spontaneously)
Drug related cheilitis Rare Drugs Emollients
Drug elimination if possible

clear criteria2. Although there are many recent papers
on cheilitis, they are mostly case reports and overviews
of therapeutic or diagnostic procedures based on per-
sonal experiences and results without specific criteria
for classification. Since clear classification has not yet
been established, there are no definitive recommenda-
tions for diagnosing all different types of cheilitis.
Apart from that, cheilitis is also a disease that requires
a multidisciplinary approach, which additionally
complicates adoption of a classification system. We
would like to put forth a classification of cheilitis into
three main groups with further particular subtypes
(Table 1).
Reversible Cheilitis
We specify reversible cheilitis (transitory cheilitis
of temporary duration) as a distinct category, which
includes several subtypes (Table 2).
Cheilitis simplex (chapped lips, common cheilitis,
cheilitis sicca) is one of the most common subtypes,
presenting as cracked lips, fissures or desquamation of
the lips, usually of the lower lip (Fig. 1)2,7. Here fre-
quent lip licking promotes dryness and irritation, end-
ing in separation of the mucosa and cracking. Some
authors use a different label for a similarly categorized
subtype, lip licking cheilitis, due to lip licking habit or

Acta Clin Croat, Vol. 57, No. 2, 2018 343

Liborija Lugović-Mihić et al.
Fig. 1. Cheilitis simplex.
frequent lip retraction into the oral cavity (especially in
children with atopic dermatitis)6,7. Such licking re-
moves the thin, oily surface film that protects the lips
from moisture loss, leading to lip cracking. Lip lesions
are also influenced by saliva, the digestive enzymes of
which can irritate the lips by extracting moisture and
causing evaporation. Some children have the habit of
sucking and biting the lower lip, whereby a sharply
bordered perioral erythema may occur.
Differential diagnosis includes contact cheilitis,
atopic cheilitis, actinic cheilitis, etc.2,4. Therapy mostly
involves advice on dealing with environmental condi-
tions and the application of lip balms, petroleum jelly,
emollients and sometimes topical corticosteroids,
mostly low potency ointments.
Angular cheilitis (also termed perleche, cheilosis, or
angular stomatitis or angulus infectiosus) typically
manifests at the corners of the mouth/lips. The disease
is most common in patients with deep wrinkles in lip
angles and those who are prone to licking lip corners8.
Generally, the disease starts during vitamin and min-
eral deficiencies (B vitamins, iron, zinc, etc.), or is
caused by other conditions and diseases (e.g., poorly
fitting dentures and drooling, celiac disease)4,6,9. An
important factor is also saliva production, i.e. increased
secretion and drooling, which contributes to the dis-
ease. Conversely, during decreased saliva secretion (hy-
posalivation), dryness promotes cracking and desqua-
mation, as well as the invasion of Candida albicans with
the emergence of angular cheilitis inflammation.
Angular cheilitis occurs more commonly in diabet-
ics, in patients with some psychiatric disorders (e.g., lip
trauma in bulimics or in anorexia nervosa), during cer-
344
Differential diagnosis of cheilitis
Fig. 2. Contact/eczematous cheilitis.
tain drug therapy (e.g., isotretinoin), and somewhat
less frequently in primary hypervitaminosis A. It is
more common during winter when additional lip lick-
ing worsens the condition, and in elderly persons2,5. It
can occur in patients with inflammatory bowel dis-
eases such as Crohn’s disease and ulcerative colitis10.
This subtype sometimes develops as part of a group
of symptoms, which can include atrophic glossitis,
esophageal webs or strictures, and microcytic hypo-
chromic anemia (Plummer-Vinson syndrome)11. Con-
currence of bacterial or candidal infection (primary or
secondary) is common2. Children, especially those
with atopic dermatitis, are most commonly affected by
secondary bacterial infections (staphylococcal and be-
ta-hemolytic streptococcal) on damaged lip corners.
Angular cheilitis with secondary infections often oc-
curs also in patients with macroglossia (congenital hy-
pothyroidism and Down syndrome).
Differential diagnosis for this type of cheilitis in-
cludes recurrent herpes labialis (if lesions are unilater-
al) and secondary syphilis (fissured papules at the cor-
ners of the lips similar to cheilitis)2,9. Therapy includes
elimination of predisposing factors and often topical
antimycotics, antiseptics, antibiotics, and sometimes
corticosteroids.
Contact/eczematous cheilitis is an inflammatory lip
reaction caused by the irritating or allergic effects of
various substances found in many products such as lip-
sticks, oral hygiene products (toothpastes), food (e.g.,
eggs and crustaceans), ointment bases, fragrances, pre-
servatives, antioxidants, dyes, dental materials, musical
or occupational instruments, objects put in the mouth
daily (e.g., nails, needles, pens), etc.7,12. It manifests as
Acta Clin Croat, Vol. 57, No. 2, 2018
Liborija Lugović-Mihić et al.
dryness, scaling, erythema or fissuring, more common-
ly on the skin than on mucosa (Fig. 2)2,13,14. This type of
cheilitis usually presents in patients with atopic der-
matitis15. Some authors use the term cheilitis venenata,
which specifically indicates contact reaction, most
commonly of an allergic type.
There is a broad spectrum of products with com-
mon irritants and allergens associated with this sub-
type. Contact reactions to lipsticks, rubber, leather ob-
jects, nail polish substances (e.g., formaldehyde), met-
als (nickel, cobalt, gold) and topical antibiotics have
been shown to be some of the more frequent etiologic
factors7,12. Reactions to compounds in topical medica-
tions and medical products, such as topical antibiotics,
virostatic agents, disinfectants, local anesthetics, and
sunscreens are also possible. Factitial cheilitis stands
out as a distinct subtype of contact cheilitis, usually
triggered by a stressful event (possible self-damaging
behavior).
Use of the patch test is important to determine
these cheilitis causing allergens and to identify the
etiologic allergen7. Patch testing usually starts with the
European baseline series and an overview of the pa-
tient’s personal cosmetic and topical products, the re-
sults of which mostly reveal contact allergens3. Ac-
cording to recent patch testing results in patients with
non-actinic cheilitis, reported by O’Gorman and
Torgerson, the most significant allergens were fra-
grance mixes, Myroxilon pereirae resin, dodecyl gallate,
octyl gallate, and benzoic acid13. According to these
results, relevant allergens in those patients were fra-
grances, antioxidants, preservatives and metals (nickel
and gold).
Differential diagnosis of contact/eczematous chei-
litis includes cheilitis simplex, exfoliative cheilitis,
among other types of cheilitis. In the treatment, most
important is to exclude etiologic factors. Therapy in-
cludes mostly topical corticosteroids of low to medium
potency and emollients, which may be combined.
Exfoliative cheilitis indicates lip inflammation, ac-
companied by constant desquamation, more common-
ly found on just one lip, usually the lower one. This
form occurs a bit less frequently than others, and is
common among young people who frequently mois-
turize their lips, followed by people with vitamin B12 or
iron deficiency, oral candidiasis, patients with allergies
(e.g., to balsam of Peru) or patients with HIV in whom
it is often associated with candida infection16-18. Exfo-
Acta Clin Croat, Vol. 57, No. 2, 2018
Differential diagnosis of cheilitis
liative cheilitis presents with continuous peeling of the
vermilion (lip border). Initially, lips may usually look
normal or red, followed by development of a thickened
surface layer, which leads to peeling that may be cyclic
and proceeds at different rates and at different sites.
Sometimes bleeding occurs, later followed by the for-
mation of a hemorrhagic crust. The disease may prog-
ress due to several factors, e.g., open-mouthed breath-
ing, lip licking, sucking, picking, or biting, bacterial
(Staphylococcus aureus) or yeast (Candida albicans) in-
fection, poor oral hygiene, etc.1. Some use the term
exfoliative cheilitis as an equivalent to cracked lips,
which increases confusion around nomenclature.
Differential diagnosis includes contact cheilitis,
cheilitis simplex, etc. Therapy includes topical cortico-
steroids, topical calcineurin inhibitor, topical Calen-
dula officinalis L., and in some cases psychotherapy1,18.
Occasionally, lesions resolve spontaneously.
Drug-induced cheilitis refers to lesions due to drug
intake, mainly retinoids (e.g., isotretinoin, acitretin) or
other medications (topical antibiotics, virostatic agents,
lip care products, disinfectants, local anesthetics,
creams with protection factors, etc.)19. Also possible
are drug reactions on skin and lips, in the form of li-
chenoid reactions, fixed drug eruptions, or changes re-
sembling erythema multiforme2,19. Emollients are cru-
cial in the treatment, and discontinuation of the of-
fending agent when possible.
Irreversible Cheilitis
This group contains a number of chronic cheilitides
the verification of which usually calls for biopsy and
histology (Table 3).
Actinic (solar) cheilitis (actinic cheilosis, sailor’s lip)
(Fig. 3) is damage to the lower lip and considered to be
a potentially malignant disorder. It is caused primarily
by exposure to ultraviolet radiation, thus it is common-
ly found in certain groups of workers (sailors, agricul-
tural workers, construction workers, beach workers,
etc.)20-24. When erosions are a predominant symptom
of the condition, then the term cheilitis abrasiva prae-
cancerosa is used.
This disease occurs mostly in middle-aged, fair-
skinned men and is a potentially malignant condition
that requires biopsies to exclude severe dysplasia or
cancer5. Clinically, the disease manifests with painless
thickening and whitish discoloration at the borders of
345
Liborija Lugović-Mihić et al. Differential diagnosis of cheilitis

Table 3. Common features of mostly persistent cheilitis

Mostly persistent
Occurrence Related factors Therapy
cheilitis
Actinic cheilitis Rare Sun damage Topical low to medium potency
(outdoor workers, corticosteroids or 5-fluorouracil, chemical peel
middle-aged fair-skinned men) cryotherapy, electrosurgery, vermilionectomy,
immunosuppressants, and surgery
Granulomatous Rare Other granulomatous diseases Topical, intralesional (e.g., repeated
cheilitis triamcinolone acetonide 2.5-5.0 mg/mL)
and systemic corticosteroids and/or antibiotics
Glandular cheilitis Very rare Smoking, poor oral hygiene, Systemic antibiotics and topical, intralesional
external influences (sunlight) or systemic corticosteroids, or surgical excision
Plasma cell cheilitis Very rare Unknown Topical and intralesional corticosteroids,
destructive measures, or sometimes even
immunosuppressants

the lips and skin. Consequently, the lip border (vermil-

ion border) becomes less clear and the lips may gradu-
ally become scaly and indurated. The lesions are usu-
ally persistent and therefore require biopsy for disease
verification. Histopathologically, epithelial atrophy oc-
curs first without cytologic atypia but with solar elas-
tosis of adjacent skin, while later squamous cell carci-
noma in situ develops with cytologic atypia, epithelial
atrophy or hyperplasia, followed by strands of epithe-
lium growing down into the lamina propria2. There-
fore, severe dysplasia is characterized by dyskeratosis
and keratin pearls, nuclei changes (hyperchromasia,
nuclear pleomorphism, anisonucleosis, increased num-
Fig. 3. Actinic cheilitis (a photo from ref. 23;
bers of nucleoli and mitoses, atypical mitoses)25. There
with the author’s permission and by the courtesy
are recent data that indicate, according to Fourier of Professor Mravak-Stipetić).
transform infra red (FT-IR) spectroscopy, that chang-
es in collagen and nucleic acids could be used as mo-
lecular biomarkers for malignant transformation20. etiology, which usually starts in young adults and pres-
Differential diagnosis of actinic cheilitis includes a ents with intermittent or permanent lip swelling (Fig.
number of diseases, i.e. epithelial dysplasia, squamous 4)5,26-28. The cause of granulomatous cheilitis has not
cell carcinoma, malignant melanoma, basal cell carci- yet been fully elucidated, but current hypothesis holds
noma, keratoacanthoma, glandular cheilitis, herpes la- that random influx of inflammatory cells is responsi-
bialis, discoid lupus erythematosus, etc. Therapy is re- ble. Other proposed related factors of the disease in-
quired to relieve symptoms and to prevent develop- clude dietary allergens such as cinnamon and benzo-
ment of squamous carcinoma. It includes topical low ates26.
to medium potency corticosteroids, 5-fluorouracil, The disease can occur as Miescher’s isolated granu-
chemical peel, cryotherapy, electrosurgery, vermilion- lomatous cheilitis or with other granulomatous dis-
ectomy, immunosuppressants, surgery, and also sun- eases (Crohn’s disease, sarcoidosis and Melkersson-
screens (sun protection). Rosenthal syndrome)5,7. Melkersson-Rosenthal syn-
Granulomatous cheilitis (or orofacial granulomato- drome is characterized by granulomatous cheilitis, fa-
sis) is chronic granulomatous lip swelling of unknown cial palsy and plicated tongue, although only one or

346 Acta Clin Croat, Vol. 57, No. 2, 2018

Liborija Lugović-Mihić et al.
Fig. 4. Granulomatous cheilitis.
two symptoms usually appear (the complete triad of
symptoms occurs in only 25% of patients). Granulo-
matous cheilitis accompanied by persistent intraoral
aphthae may suggest Crohn’s disease.
Histologically, granulomatous cheilitis is charac-
terized by chronic inflammatory reaction consisting of
lymphocytes, histiocytes, and tuberculoid granuloma
having epithelioid cells and Langerhans giant cells27.
Histology from early lesions shows only edema and
sparse infiltrate, while later there is a more intense in-
filtrate with small sarcoidal granulomas. Differential
diagnosis of granulomatous cheilitis includes elephan-
tiasis nostras, forms of recurrent erysipelas and herpes
simplex, macrocheilia, angioedema, tuberculosis, glan-
dular cheilitis, contact cheilitis, Ascher’s syndrome, or-
ganized hematoma, sarcoidosis, among others14,26,27.
Therapy may include topical, intralesional (e.g., triam-
cinolone acetonide 2.5-5.0 mg/mL for several months
or longer) and systemic corticosteroids/antibiotics, di-
etary modifications and surgery, although treatment is
not always necessary26,28.
Glandular cheilitis is a rare chronic inflammatory
condition of the minor salivary glands, predominantly
of the lower lip2,29. The disease was first described by
von Volkmann under the designation ‘cheilitis glandu-
laris apostematosa’ or ‘myxadenitis labialis’29. Etiologic
factors considered to be involved are smoking, poor
oral hygiene, chronic exposure to external influences
(sunlight, wind, tobacco), bacterial infection and con-
genital predisposition.
Variants are cheilitis simplex and cheilitis apostema-
tosa. The simplex form usually manifests as tiny red
papules, especially on the lower lip, with a possible,
Acta Clin Croat, Vol. 57, No. 2, 2018
Differential diagnosis of cheilitis
gradually evolving lip edema (macrocheilia). It can be
related to chronic irritation of the lower lip (actinic,
atopic or mechanical), with potential secondary causes
being chronic sialadenitis, ductal metaplasia and fibro-
sis. Glandular apostematosa cheilitis is a secondary
staphylococcal infection of the minor salivary glands,
which presents with crust and pus drainage accompa-
nied by pain.
Histopathology is nonspecific with possible sali-
vary gland hyperplasia, duct ectasia, and dermal in-
flammatory infiltrate (lymphocytes, plasma cells, his-
tiocytes). Differential diagnosis includes other forms
of cheilitis and squamous cell carcinoma. Management
includes histopathologic analysis, identification of eti-
ologic factors, and attempts to alleviate or eradicate
these factors. Therapy includes systemic antibiotics
and topical, intralesional or systemic corticosteroids, or
surgical excision.
Plasma cell cheilitis is a very rare type of lip inflam-
mation of unknown etiology characterized histologi-
cally by diffuse plasma cell infiltration in dermis27,30.
Clinically, it presents as a circumscribed and flat to
slightly raised eroded area of the lip, or as erythema-
tous-violaceous, ulcerated and asymptomatic plaques
which evolve slowly. Histology includes a band-like
infiltrate of plasma cells in the upper dermis, with pos-
sible capillary dilation, erythrocyte extravasation, he-
mosiderin deposits, and mild epidermal spongiosis.
Differential diagnosis includes actinic cheilitis, allergic
contact cheilitis, lichen planus, etc. Therapy may in-
clude topical and intralesional corticosteroids, topical
calcineurin inhibitors, destructive treatment methods,
or sometimes even immunosuppressants30.
Cheilitis Associated with Skin Diseases
and Systemic Diseases
The chronic discoid form of lupus erythematosus can
sometimes encompass lip changes/lesions, which pres-
ent as diffuse cheilitis, spreading usually above the ver-
milion zone. Subacute cutaneous lupus erythematosus
rarely includes oral lesions, manifesting with sharply
bordered, slightly atrophic erythema of oral mucosa or,
as in severe cases, a diffuse erythematous, scar plaque,
which extends beyond the vermilion. Lip changes in
systemic lupus erythematosus may present as bordered
or diffuse erythema, purpuric maculae, erosions or ul-
cerations, or patients may have oral ulcerations, which
347
Liborija Lugović-Mihić et al.
Fig. 5. Lip lesions/cheilitis in association with pemphigus
vulgaris.
are one of the major criteria for systemic lupus erythe-
matosus diagnosis31. Generalized rash in acute lupus
can also affect the lips in some cases. Differential diag-
nosis of lupus erythematosus on the lips may include
allergic contact dermatitis, actinic cheilitis, lichen pla-
nus, psoriasis, erythema multiforme, pemphigus vul-
garis, squamous cell carcinoma, etc.
Lichen planus as a chronic mucocutaneous disease
occurs in 6% of cases on the lips in the form of reticu-
lar, striatus or annular Wickham’s striae, irregular
(patchy) erythema and erosions, especially of the lower
lip32. Differential diagnosis includes lichenoid drug re-
actions (e.g., to antiinflammatory medications, angio-
tensin-converting enzyme inhibitors, antimalarials),
lichenoid contact dermatitis (e.g., to amalgam and
other dental materials), discoid lupus erythematosus,
etc.
Angioedema manifests often on the lips and is
mostly allergic19,33. It is one of the most common
causes of transient lip swelling, while macrocheilia de-
scribes permanent swelling of one or both lips.
Manifestations of bullous diseases are also possible
on the lips, especially in pemphigus vulgaris (Fig. 5), an
autoimmune mucocutaneous blistering disease the ini-
tial manifestations of which often are oral lesions (50%
to 70% of cases), mostly erosions. Similar changes may
be seen in the pemphigoid group34. Sometimes it ini-
tially presents with single persistent lower lip lesions
without progressing to other location. Both the pem-
phigus and pemphigoid workups are complex and in-
clude histopathologic and immunofluorescent diag-
nostics.
348
Differential diagnosis of cheilitis
Fig. 6. Lip lesions/cheilitis in association with erythema
multiforme.
Lips may also be affected as part of other dermato-
ses, e.g., erythema multiforme (Fig. 6), atopic dermati-
tis, herpes simplex, Stevens-Johnson syndrome, and
toxic epidermal necrolysis, often resulting in the for-
mation of erosions and crusts2,19.
Discussion
Cheilitis is a term describing lip inflammation of
various etiologies, which occurs relatively often. The
disease may appear as an isolated condition or as part
of certain systemic diseases or conditions. It may be
part of a clinical picture or an accompanying condi-
tion. Cheilitis can co-occur with many conditions in-
cluding anemia, oral candidiasis, atopy, contact reac-
tion to an irritant or allergen (e.g., to cosmetics), drug
intake (e.g., retinoids), etc. Generally, the most com-
monly reported forms in the literature are angular,
contact (allergic and irritant), actinic, exfoliative,
etc.2,21-24. As contact cheilitis can be related to the ef-
fects of irritants or allergens, it should be investigated
with thorough history taking. Some lip lesions require
biopsies, such as chronic actinic cheilitis (to examine
for severe dysplasia or cancer) or granulomatous chei-
litis (to confirm the diagnosis)5,22,35.
When managing and diagnosing cheilitis, com-
plete examination of the patient’s oral cavity, skin and
other mucosae is required, along with appropriate di-
agnostic procedures. When approaching patients, sev-
eral factors need to be taken into account, particularly
patient general medical history (e.g., existence of dia-
betes, atopy, immunosuppression), exposure to external
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Liborija Lugović-Mihić et al. Differential diagnosis of cheilitis

Table 4. Common diagnostic parameters/procedures related to specific cheilitis group

In association with
Mostly persistent
Mostly reversible dermatoses and
(irreversible)
systemic diseases
– History data: drug intake, habits (lip licking, biting, sucking, picking, Persistent lesions Diagnostic
etc.), weather conditions (cold, hot, windy, dry weather), age, poor oral require biopsy work-up according
hygiene, open-mouthed breathing, related diseases/conditions and to suspected disease
(e.g., diabetes, psychiatric disorders, atrophic glossitis, dysphagia, histopathologic
esophageal webbing, etc.) analysis
– Deficiencies, e.g., B vitamins (B2, B3, B5, B7, B12), iron, zinc, etc.,
malnutrition (e.g., celiac disease), or hypervitaminosis (e.g., vitamin A)
– Atopy (in patient and family): total IgE, allergic skin tests
(patch test, prick test), in vitro allergic tests
– Oral and skin swabs (mycotic and bacterial; e.g., yeast infection such as
Candida albicans or bacterial infection such as Staphylococcus aureus
or Streptococcus)

factors (e.g., weather conditions), the possibility of vi-
tamin or mineral deficiencies, undesirable habits (lip
licking, frequent sun exposure, lip contact with various
substances), etc. (Table 4). It is also important to know
whether the lesions are persistent or whether they are
reversible since irreversible cheilitis demands a differ-
ent treatment approach.
Until now, there have been no clear recommenda-
tions for the workup and classification of cheilitis al-
though cheilitis has been identified and recognized for
quite a long time. In the literature on cheilitis, varied
nomenclature is used and subtypes are grouped and
named differently. Braun Falco et al., for instance, clas-
sify cheilitides as angular, simplex, actinic (acute/
chronic), glandularis, granulomatous and plasma cell
cheilitis2. According to the PUBMED/MEDLINE
database, the total number of published articles re-
trieved by the keywords ‘cheilitis classification’ does
not exceed 14 while those searched by the keywords
‘differential diagnosis’ does not exceed 120. Regarding
newly published articles, most are case reports and
overviews of therapeutic or diagnostic procedures
based on personal experiences and results. Taking into
account our experience and that of other authors, we
are offering an overview of the most important cheili-
tis types. According to Oakley, there are few cheilitis
groups: (1) cheilitis due to infection or skin conditions
(angular, granulomatous, orofacial granulomatosis,
Crohn’s skin disease, actinic, exfoliative, glandular, li-
chenoid, cutaneous lupus erythematosus); (2) cheilitis
due to an allergy, toxin, medication or injury (eczema-
tous cheilitis, allergic contact cheilitis, pigmented con-
tact cheilitis, cheilitis in musicians, contact reactions to
lipsticks and other lipcare products, irritant and aller-
gic contact dermatitis, smoking and its effects on the
skin, sunburn, isotretinoin treatment, acitretin treat-
ment, denture stomatitis); and (3) cheilitis due to nu-
tritional deficiency (iron, vitamin B)4.
According to our experience and clinical practice,
we suggest the classification of cheilitis as (1) mainly
reversible (transient); (2) mainly irreversible (persis-
tent); and (3) cheilitis associated with particular der-
matoses and systemic diseases (Table 1). This kind of
classification would be based upon primary differences
in the course and etiology of individual groups of chei-
litides. Thus, the group of reversible cheilitides (of
temporary duration) includes mostly milder types of
cheilitis, which usually significantly regress following
elimination of the etiologic factor. Rarely they are per-
sistent and resistant to treatment. Cheilitides of the
irreversible type have a more lasting character, which
usually requires histologic workup (biopsy). Finally,
the third class of cheilitides encompasses inflamma-
tory lip changes related to specific skin or systemic dis-
eases.
There are no precise epidemiologic data on the
prevalence and incidence of each cheilitis type either.
We can only give data on its frequency based on our
clinical experience. The approach to cheilitis needs to
be interdisciplinary and should include dermatolo-

Acta Clin Croat, Vol. 57, No. 2, 2018 349

Liborija Lugović-Mihić et al.
gists, oral pathologists, ENT specialists, and also spe-
cialists in internal medicine and psychiatry1,6,7,10,19,26,36-39.
Professionals from different specialties can come to a
conclusive diagnosis by additional specific diagnostics.
It is important to have in mind that the approach to a
patient with cheilitis includes, apart from dermato-
logic conditions, other related diseases such as some
granulomatous diseases (Crohn’s disease, sarcoidosis
and Melkersson-Rosenthal syndrome), nutritional de-
ficiencies, and gastrointestinal diseases (e.g., celiac dis-
ease, Plummer-Vinson syndrome) (Table 4).
We find that our classification would mean consid-
erable benefit for patients and hasten treatment since
it would simplify recognition and diagnosis, thereby
ensuring appropriate treatment. We found that the
crucial step is getting detailed medical history of the
patient with all possible information on the potential
mitigating factors. Complete medical history, clinical
picture and appropriate diagnostic workup are the key
factors in recognizing the right type of cheilitis and of
its successful treatment.
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Sažetak

DIFFERENCIJALNA DIJAGNOZA HEILITISA – KAKO KLASIFICIRATI HEILITIS?

L. Lugović-Mihić, K. Pilipović, I. Crnarić, M. Šitum i T. Duvančić

Iako je heilitis kao pojam koji opisuje upalu usnica bio zapažen i prepoznat već prije dugo vremena, dosad nema jasnih
preporuka za dijagnostički postupak i klasifikaciju. Bolest se može javiti kao izolirano stanje ili kao dio nekih bolesti/stanja
poput anemije (zbog nedostatka vitamina B12 i željeza) ili lokalne infekcije (npr. herpes i oralna kandidijaza). Heilitis također
može biti simptom kontaktne reakcije na iritans ili alergen te može biti potaknut izlaganjem suncu (aktinički heilitis) ili
uzimanjem lijeka (osobito retinoida). Općenito se najčešće spominju oblici angularni, kontaktni (alergijski i iritativni), akti-
nički, glandularni, granulomatozni, eksfolijativni i plazmacelularni heilitis. Ipak se u literaturi o heilitisu rabi različita nomen-
klatura pa su podtipovi grupirani i nazvani različito. Prema našem iskustvu i kliničkoj praksi predlažemo klasifikaciju teme-
ljenu na primarnoj razlici u trajanju i etiologiji pojedinih skupina heilitisa: 1. pretežno reverzibilni (simpleks, angularni/in-
fektivni, kontaktni/ekcematoidni, eksfolijativni, lijekom potaknuti), 2. pretežno ireverzibilni (aktinički, granulomatozni,
glandularni, plazmacelularni) i 3. heilitisi povezani s dermatozama i sustavnim bolestima (lupus, lihen planus, skupina pem-
figusa/pemfigoida, angioedem, kserostomija itd.).
Ključne riječi: heilitis; upala; usna, bolesti; aktinički heilitis; klasifikacija; dermatitis, kontaktni

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